Breakfast skipping and cardiometabolic risk factors in adolescents: Systematic review

ABSTRACT OBJECTIVE To systematically review the results of the association between breakfast skipping and cardiometabolic risk factors in adolescents. METHODS The articles were searched in May 2020 from PubMed, Virtual Health Library, Scopus, Web of Science and Scientific Electronic Library Online (SciELO). The review included observational studies conducted with adolescents (10–19 years old), which estimated the association of breakfast skipping with at least one outcome (markers of body adiposity, blood pressure, serum lipid and glucose levels). Regarding the risk of bias, the articles were evaluated using the Research Triangle Institute (RTI) Item Bank on bias risk and accuracy of observational studies. The quality of the evidence was assessed by the Grade rating. RESULTS A total of 43 articles involving 192,262 participants met the inclusion criteria and were considered in this review. The prevalence of breakfast skipping ranged from 0.7% to 94% and 60.5% of studies were classified with low risk of bias. The significant association between breakfast skipping and cardiometabolic risk factors was found in twenty-nine cross-sectional articles (n = 106,031) and four longitudinal articles (n = 5,162) for excess adiposity, in three articles (n = 8,511) for high total cholesterol levels, low-density lipoprotein and triglycerides, and in three studies (n = 6,303) for high blood pressure levels. However, there was no significant association between breakfast skipping and glycemic profile. According to the Grade rating, all the associations had low quality of evidence. CONCLUSION The results of this review suggest that breakfast skipping is associated with cardiometabolic risk factors in adolescents aged 10 to 19 years. However, considering the low quality of the evidence, the present results should be interpreted carefully. In addition, our findings highlight the importance of standardizing the definition of breakfast skipping and that more prospective studies are needed to determine how skipping breakfast can affect cardiometabolic risk factors in the long time.


INTRODUCTION
In recent decades, the meal consumption pattern has been associated with adolescents' physical growth and various health outcomes 1 . Among behaviors related to that, we highlight the unfavorable effect of skipping meals, especially breakfast 1 . Outcome not evaluated.
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Wang et al. 16 New Haven Outcome not evaluated.
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Cayres et al. 22 Brazil n = 86 11-14 years F 51.2% Period 3 : 12 months. "How many days a week do you usually have breakfast? Zero (score 0) a . 1 to 2 days (score 1) a 3 to 5 days (score 2) a Every day of the week (score 3).
Sex, age and level of sexual maturation.
Not shown. At the beginning of the study, adolescents who skipping breakfast had higher BMI (p = 0.032), abdominal fat (p = 0.019) and total body fat (p = 0.012) than those who ate breakfast regularly. of adolescents who skipped breakfast increased more than those who ate regularly.
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Hassan et al. 23 Brazil Outcome not evaluated.
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(Low).
Deshmukh-Taskar et al. 34 United States of America Outcome not evaluated.
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(Low
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Skipped breakfast
Did not skip breakfast.
Not adjusted. 23.6% There was no significant association between breakfast skipping and overweight (p = 0.992).
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(Low).
Mustafa et al. 60  Study follow-up period; 4 Only 2 participants of 20 years and were classified with normal weight.
(10-19 years old, as defined by the World Health Organization) 18 , which have estimated the association of breakfast skipping with at least one of the cardiometabolic risk factors (markers of body adiposity, blood pressure, systemic arterial hypertension, serum lipid, and glucose levels).
The articles including adolescents with mental disorders, kidney disease, HIV, cancer, Down syndrome, and others were excluded from the review; those including other age groups, in addition to individuals aged between 10 and 19 years, and articles that did not present separate results for this age group; non-empirical records, opinions and editorials, case studies, summaries of scientific events that were not published as full papers, intervention studies and animal studies were also excluded.

Review Process
The articles were selected by two independent researchers and disagreements were discussed and analyzed at subsequent meetings. After the search, the Mendeley reference management tool was used to exclude duplicate records, and an initial screening was performed to reject records whose title and/or abstract information failed the inclusion criteria. If abstracts were unavailable or provided insufficient results, the article was selected for full reading. After analyzing the articles previously selected for full reading, reviewers included studies with results on the association of breakfast skipping with cardiometabolic risk factors (Figure). The studies were presented according to the following characteristics: (1) identification data with citation of the author(s), year of publication and place of study; (2) number of individuals evaluated, age and sex of the sample studied; (3) study outcome(s); (4) breakfast skipping assessment; (5) control of confounding factors and (6) main results (prevalence of breakfast skipping, association of breakfast skipping with markers of body adiposity, serum lipid levels, glucose metabolism (insulin resistance, fasting glucose and glucose intolerance) and blood pressure). Table 1 shows this information in chronological order.

Evaluation of Study Quality
The studies included in this systematic review underwent independent quality and risk of bias review by two reviewers. The instrument used was the Research Triangle Institute (RTI) Item Bank on Bias Risk and Accuracy of Observational Studies proposed and validated by Viswanathan & Berkman 19 to assess risk of bias and accuracy of observational studies.
The RTI Item Bank includes several study designs, and the authors provided instructions on which items to use depending on the studies being evaluated. Considering the authors' recommendations and the types of study included in this review, ten items were used to evaluate cross-sectional studies (sample definition and selection, consistency of information, outcomes, comparability of analysis, analysis results, interpretation of results, and funding) and thirteen items for cohort studies (three additional questions on follow-up time and impact of losses). Thus, a cross-sectional study with three or more key items classified as negative or unclear or a cohort study with four or more negative or unclear items were classified as at risk of bias ( Table 1).

Evaluation of the Quality of Evidence
This evaluation aims to provide greater reliability to the critical analysis of the findings. In this study, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used for each analyzed outcome 20 . The following criteria were used to evaluate the studies: design (randomized clinical trial starts with high quality and observational study with low); factors responsible for reducing evidence level (methodological limitations, indirect evidence, imprecision, and publication bias) and factors that contribute to raising the evidence (large magnitude of effect, dose-response gradient, and residual confounding factors). After evaluation according to the GRADE rating, the studies were classified into four quality of evidence levels: High (A) -There is strong confidence that the true effect/association is close to that estimated; Moderate (B) -There is moderate confidence in the estimated effect/association; Low (C) -Confidence in the effect/association is limited; and, Very low (D) -Confidence in the effect/association estimate is very limited 20 (Table 2).

RESULTS
In the databases searched, 4,660 records were identified and 3,910 remained after deletion of duplicates. Then, the titles and abstracts were read, and 134 articles were selected for full reading, of which 91 did not meet the inclusion criteria; therefore, a total of 43 articles were included in this systematic review (Figure).  (Table 1).
Four studies found significant association between breakfast skipping and markers of body adiposity 11,16,21,22 , that is, adolescents who skipped breakfast showed an increase in BMI, and body and abdominal fat over time. The analyzes were adjusted for potential confounding factors related to sociodemographic, economic, lifestyle and sexual maturation characteristics (Table 1).
Among the articles included in this review, eight evaluated the association of breakfast skipping with cardiometabolic risk factors (glucose metabolism, blood pressure, and serum lipid levels), all of which are cross-sectional 12,29,31,41,49,56,58,60 .
Of these studies, five investigated the association between breakfast skipping and lipid profile 12,41,49,56,60 , and three found a statistically significant association; therefore, adolescents who omitted breakfast had higher levels of total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) 12,41,60 . Five of the eight articles investigated the association between breakfast skipping and glycemic profile (fasting glucose, Homeostatic Insulin Resistance Assessment Model (HOMA-IR), acute insulin response, and insulin sensitivity), but none of them found a significant association 29,41,56,58,60 .
Regarding blood pressure, five articles evaluated the association between breakfast skipping and high blood pressure 31,41,49,56,60 ; and three found a significant association, i.e., adolescents who skipped breakfast had higher levels of systolic blood pressure (SBP) 31,41,49 .
In summary a significant positive association for lipid profile and blood pressure was found, whereas for glycemic profile there was no association, all risk factors were rated GRADE C.

DISCUSSION
This systematic review included 43 studies that evaluated the association between breakfast skipping and cardiometabolic risk factors in adolescents. The prevalence of breakfast skipping varied widely between studies. Adolescents who skipped breakfast were more likely to have cardiometabolic risk factors, e.g., excess adiposity, higher levels of total cholesterol, low density lipoprotein, triglycerides, and blood pressure. However, the association between breakfast skipping and glycemic profile is unclear, since only five studies were included, and none found a significant association. The impact of the content of macronutrients present at breakfast 29 and adjustment for body adiposity 29,41,58,60 , and quality of diet 60 can explain those associations.
Of the studies, 78.4% found that breakfast skipping is associated with excess body fat in adolescents. Intiful and Lartey 61 attribute this association to adolescents who omit breakfast being more likely to eat other meals, such as lunch and dinner, irregularly and to eat unhealthy food between meals, such as non-nutritious snacks and fast foods. Thus, adolescents who skip breakfast consume more fat and less fiber, vitamins, and minerals 4 and are less physically active, leading to an imbalance between energy consumption and expenditure 62 .
Wang et al. 16 and Cayres et al. 22 showed that breakfast skipping is associated with weight gain, since adolescents who skipped this meal spent a longer period fasting (night and morning), with increased ghrelin release 63 , consequently, increased appetite, increasing the probability of hyperphagia and body fat accumulation 64 .
A potential confounding factor in assessing the association between breakfast skipping and body adiposity is energy intake, since individuals who skip breakfast tend to consume high energy density foods, or they may consume more energy from other meals throughout the day 16,49 . Four studies in this review evaluated the association of breakfast skipping with body adiposity, adjusting for total energy consumption; in three of them, the association remained even after adjustment 21,29,34 .
Three articles found an association between breakfast skipping and abnormal lipid profile 12,41,60 in addition to the observed propensity for excess body adiposity. The main factors that may explain this association are related to increased appetite and high energy intake after fasting 12 . Breakfast skipping also induces insulin resistance and may play an important role in the development of dyslipidemia 65 . Hyperinsulinemia may increase apolipoprotein B-48 secretion by stimulating chylomicrons formation in the small intestine and inducing postprandial hyperlipidemia. Next, lipoprotein lipase, which hydrolyzes the central chylomicrons triglycerides 66 , is inhibited, leading to increased hepatic lipase activity, which hydrolyzes LDL-cholesterol and HDL-cholesterol, triggering the decrease in HDL-cholesterol and the increase of small and dense LDL-cholesterol arterial particles 67 .
Regarding blood pressure increase in adolescents who omit breakfast, three articles in this review found a significant association 31,41,49 . The mechanisms that explain this association are still unclear, but they seem to be related to body adiposity, which may be the result of skipping breakfast, as mentioned above. Vanderlei et al. 68 argue that increased body fat is related to higher sympathetic activity, because adiposity is associated with increased oxidative stress, increasing stimulation in specific brain regions that control sympathetic activity 69 . However, the associations found by Kollias et al. 31 , Shafiee et al. 41 , and Cayres et al. 49 remained significant for SBP, even after adjustment for indicators of body adiposity.
The five articles that evaluated breakfast skipping and glucose metabolism-related variables found no significant association 29,41,56,58,60 . Alexander et al. 29 reported that this association was not supposed to be found by the impact of the macronutrient content in breakfast on metabolic parameters, but the study did not evaluate the type of breakfast, therefore, its influence in the results cannot be stated. According to Tolfrey and Zakrzewski 70 , breakfast with high-fiber, low-glycemic cereals is associated with increased glycemic control and satiety.
The metabolic effects of breakfast can also be explained by their impact on the circadian cycle, a period in which the environment influences the transcription of some genes, mainly by light variations and by the time of feeding, which helps synchronize this system 71 . When food is restricted during a period, such as breakfast skipping, i.e., the fasting period after the sleeping period increases, circadian cycles may be out of sync, causing changes in certain genes that regulate lipid and glucose metabolism 1 .
The variation in the results found in the articles may have been influenced by the different ways of collecting information on breakfast consumption and the definition of skipping breakfast. The definition most used by the studies considered the frequency of breakfast consumption ("rarely", "never" and number of days/week).
Dialektakou et al. 72 stressed that breakfast skipping is associated with BMI, but this association depends on how skipping is defined. Among Greek adolescents, the authors found that all variables corresponding to breakfast consumption on the day of data collection were associated with both BMI and overweight or obesity. However, few associations remained significant when considering breakfast consumption in the previous week; which may have been because adolescents' recollections of omitting breakfast in the previous week were less accurate than information reported on the day of data collection.
Among Brazilian adolescents, Hassan et al. 23 also found that the results depend on how breakfast skipping defined and on how the variable was categorized; they noted that the prevalence of breakfast skipping ranged from 3.6 % when the baseline was last week to 39.0% when we asked the teenagers if they had eaten any solid food in the morning of the interview.
In the cohort study conducted by Timlin et al. 21 with a 5-year follow-up, they considered a cutoff point of breakfast skipping every day and observed that adolescents who omitted breakfast had a greater increase in the mean BMI. Cayres et al. 22 observed similar results, which also considered the cutoff point of skipping in 5 days, follow-up was 12 months and abdominal fat and total body fat of the adolescents who skipped breakfast increased more than those who ate regularly.
Thus, the definition and standardization of the category defining breakfast skipping may influence the results and their interpretation. This systematic review found a wide variation in the definitions of breakfast skipping, hindering the comparison between the results. According to Hassan et al. 23 , a standard definition of breakfast skipping in the scientific literature is essential to improve comparisons among studies and results interpretation.
The American Heart Association recently proposed definitions to improve and standardize the assessment of consumption and skipping of meals 1 : breakfast as the first meal of the day that breaks the fast after the longest period of sleep, eaten within 2 to 3 hours of waking, consisting of food or drink from at least one food group and consumed in any location. Other meals were defined as consumption occasions that provide ≥ 15% of the total energy intake and snacks as consumption occasions that provide < 15% of the total energy intake 1 .
In addition, Food Guide for the Brazilian population 73 recommends the consumption of fresh or minimally processed foods for breakfast, such as milk, coffee, eggs, fruits, and preparations based on cereals or tubers, since the nutritional composition of this meal is important and the consumption of certain foods for breakfast can have a protective effect against cardiometabolic risk factors, such as BMI, total cholesterol, and LDL 60 .
Standardizing the definition of breakfast skipping is necessary to enable the aggregation of results and the summarization of effects, and to better evaluation and understanding of scientific evidence in the association between breakfast skipping and cardiometabolic risk factors in adolescents. This can subsidize public policies and technical advice directed to schools aiming at instructing on the effects and risks of skipping breakfast on the cardiometabolic health of adolescents and promoting the daily consumption of this meal.
The studies included in this systematic review showed a significant association with excess adiposity, lipid profile, and blood pressure. In summary, the positive association remained for these outcomes with quality, according to the GRADE rating, C -low. As for the glycidic profile, no association was observed, and the quality of evidence was also C -low. Despite the low quality of the evidence of this study's findings, we observed that they agree with what other studies with adolescents verified, thus, breakfast skipping was associated with cardiometabolic risk factors 5,10,15 . The low quality of the evidence from the studies was also mainly due to the observational design and inconsistency.
The conflicts of interest towards the financing of studies by the food industry is also important to point out. Some studies 16,41,44 were financed by the food industries that manufacture breakfast cereals and despite the researchers reporting no conflict of interest, the food industry has an interest in promoting the habit of having breakfast, because the consumption of breakfast cereals generally occurs in this meal. Breakfast cereals are also classified as ultra-processed food products, that is, they contain high levels of added sugars, salt, and unhealthy fats, thus being unhealthy. Pagliai et al. 74 systematic review and meta-analysis, which analyzed ultra-processed and chronic diseases, showed a relation between the consumption of ultra-processed products and increased risk of obesity, metabolic syndrome, and cardiovascular diseases.
The strengths of this review include the search in various databases, the selection and evaluation of articles by peers, the evaluation of the quality of the included studies and the focus only on adolescents aged 10 to 19 years old. Among the limitations is the inclusion of longitudinal studies that evaluated only the markers of body adiposity and the impossibility of performing statistical synthesis through meta-analysis, due to the different definitions of breakfast skipping and statistical analysis methodologies adopted by the studies.

CONCLUSION
The results suggest that breakfast skipping is associated with cardiometabolic risk factors in adolescents aged 10 to 19 years. However, considering the low quality of the evidence, they should be interpreted carefully. We emphasize the importance of standardizing the breakfast skipping definition for better use as an exposure factor in assessing cardiometabolic risk factors and we recommend carrying out studies with longitudinal designs to raise the level of evidence and ensure temporality and consistency of results in different confusion scenarios.